The long term aim of this work is to define the loci and mechanisms of cytogenetic variation in differentiated somatic cells, including the role of such changes in carcinogenesis. Matched sets of polyploid cells have been obtained from Chinese hamster cells and used as model systems to predict the results of specific types of spontaneous changes as well as those induced by chemical mutagens. Markers used for this purpose are those involving resistance to specific drugs such as 8-azaguanine, bromodeoxyuridine, cytosine araboside, and vinblastine. Other studies with antimitochondrial drugs (chloramphenicol, ethidium bromide, and erythromycin) are designed to see whether resistance to these agents may be mediated by heritable changes at the mitochondrial level.